New Supramolecular Hypoxia-Sensitive Complexes Based on Azo-Thiacalixarene

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Medical Diagnostics

Background:

• Hypoxia is prevalent in many human diseases and linked to tumor aggressiveness, making in vivo measurement clinically significant.
• Calix[4]arene complexes have emerged as effective hypoxia markers.
• There is a need for novel, sensitive, and selective hypoxia-targeting agents.

Purpose of the Study:

• To synthesize and characterize novel hypoxia-sensitive host-guest complexes using thiacalix[4]arene derivatives.
• To evaluate the hypoxia sensitivity and binding characteristics of these complexes with rhodamine dyes.
• To assess the stability and potential for selective hypoxia visualization in biological contexts.

Main Methods:

• High-yield synthesis of a novel thiacalix[4]arene derivative (thiacalixarene L) functionalized with anionic carboxyl azo groups.
• Complexation studies with cationic rhodamine dyes (6G, B, 123) using 1D and 2D NMR spectroscopy.
• Assessment of hypoxia sensitivity using UV-VIS spectrometry and fluorescence measurements.
• Evaluation of complex stability in biological milieu.

Main Results:

• Thiacalixarene L was successfully synthesized and formed host-guest complexes with rhodamine dyes.
• Rhodamines B and 123 formed 1:1 complexes, while rhodamine 6G formed mixed complexes with higher association constants.
• The thiacalixarene L-dye complexes demonstrated hypoxia responsiveness via UV-VIS and fluorescence.
• Complexes with rhodamine 6G and B exhibited stability in biological environments.

Conclusions:

• Thiacalixarene L exhibits stronger dye binding compared to previous azo-calix[4]arene derivatives.
• The synthesized thiacalixarene L-dye complexes show potential for selective and sensitive visualization of hypoxia.
• These findings contribute to the development of advanced diagnostic tools for hypoxia-related diseases.